Background Studies have shown that staged percutaneous coronary intervention (PCI) for non-culprit lesions is beneficial for prognosis of ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease. However, the optimal timing of staged revascularization is still controversial. This study aimed to find the optimal timing of staged revascularization. Methods A total of 428 STEMI patients with multivessel disease who underwent primary PCI and staged PCI were included. According to the time interval between primary and staged PCI, patients were divided into three groups (<= 1 week, 1-2 weeks, and 2-12 weeks after primary PCI). The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal re-infarction, repeat revascularization, and stroke. Cox regression model was used to assess the association between staged PCI timing and risk of MACE. Results During the follow-up, 119 participants had MACEs. There was statistical difference in MACE incidence among the three groups (<= 1 week: 23.0%; 1-2 weeks: 33.0%; 2-12 weeks: 40.0%; P = 0.001). In the multivariable adjustment model, the timing interval of staged PCI <= 1 week and 1-2 weeks were both significantly associated with a lower risk of MACE [hazard ratio (HR): 0.40, 95% confidence intervals (CI): 0.24-0.65; HR: 0.54, 95% CI: 0.31-0.93, respectively], mainly attributed to a lower risk of repeat revascularization (HR: 0.41, 95% CI: 0.24-0.70; HR: 0.36, 95% CI: 0.18-0.7), compared with a strategy of 2-12 weeks later of primary PCI. Conclusions The optimal timing of staged PCI for non-culprit vessels should be within two weeks after primary PCI for STEMI patients.